In the brain of Alzheimer's patient, the peptide composed of about 40 amino acids residue as is called amyloid β protein, that accumulates to form insoluble specks (senile specks) outside nerve cells is widely observed. It is concerned that this senile specks kill nerve cells to cause Alzheimer's disease. The therapeutic agents for Alzheimer's disease, such as decomposition agents of amyloid β protein and amyloid β vaccine, are under investigation.
Secretase is an enzyme which cleaves amyloid β precursor protein (APP) in cell and produce amyloid β protein. The enzyme which controls the production of N terminus of amyloid β protein is called as BACE 1 (beta-site APP-cleaving enzyme 1, β-secretase). It is thought that inhibition of this enzyme leads to reduction of producing amyloid β protein and that the therapeutic agent for Alzheimer's disease will be created by the inhibition.    Patent Literature 1 describes the compounds which are similar to those of the present invention, and the compounds have NO synthase enzyme inhibitory activity and are useful for dementia.    Patent Literatures 2 to 4 and Non-patent Literatures 1 and 2 describe the compounds which are similar to those of the present invention, and are useful for hypertensive agent, analgesic like morphine, or tranquilizers, intermediate for medicine, analgesic respectively.    Patent Literature 5 to 13 are known as BACE 1 inhibitor, however, all compounds in these literatures have different structures from the present invention.    [Patent Literature 1] International Patent Application Publication WO96/014842    [Patent Literature 2] U.S. Pat. No. 3,235,551    [Patent Literature 3] U.S. Pat. No. 3,227,713    [Patent Literature 4] JP Application Publication H09-067355    [Patent Literature 5] International Patent Application Publication WO01/187293    [Patent Literature 6] International Patent Application Publication WO04/014843    [Patent Literature 7] JP Application Publication 2004-149429    [Patent Literature 8] International Patent Application Publication WO02/96897    [Patent Literature 9] International Patent Application Publication WO04/043916    [Patent Literature 10] International Patent Application Publication WO2005/058311    [Patent Literature 11] International Patent Application Publication WO2005/097767    [Patent Literature 12] International Patent Application Publication WO2006/041404    [Patent Literature 13] International Patent Application Publication WO2006/041405    [Non-Patent Literature 1] Journal of Heterocyclic Chemistry, 14, 717-723 (1977)    [Non-Patent Literature 2] Journal of Organic Chemistry, 33, 8, 3126-3132 (1968)